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Influence of Smoking Status and Intensity on Discovery of Blood Pressure Loci Through Gene-Smoking Interactions.

ABSTRACT: Genetic variation accounts for approximately 30% of blood pressure (BP) variability but most of that variability has not been attributed to specific variants. Interactions between genes and BP-associated factors may explain some "missing heritability." Cigarette smoking increases BP after short-term exposure and decreases BP with longer exposure. Gene-smoking interactions have discovered novel BP loci, but the contribution of smoking status and intensity to gene discovery is unknown.We analyzed gene-smoking intensity interactions for association with systolic BP (SBP) in three subgroups from the Framingham Heart Study: current smokers only (N = 1,057), current and former smokers ("ever smokers," N = 3,374), and all subjects (N = 6,710). We used three smoking intensity variables defined at cutoffs of 10, 15, and 20 cigarettes per day (CPD). We evaluated the 1 degree-of-freedom (df) interaction and 2df joint test using generalized estimating equations.Analysis of current smokers using a CPD cutoff of 10 produced two loci associated with SBP. The rs9399633 minor allele was associated with increased SBP (5 mmHg) in heavy smokers (CPD > 10) but decreased SBP (7 mmHg) in light smokers (CPD ? 10). The rs11717948 minor allele was associated with decreased SBP (8 mmHg) in light smokers but decreased SBP (2 mmHg) in heavy smokers. Across all nine analyses, 19 additional loci reached P < 1 × 10(-6).Analysis of current smokers may have the highest power to detect gene-smoking interactions, despite the reduced sample size. Associations of loci near SASH1 and KLHL6/KLHL24 with SBP may be modulated by tobacco smoking.

SUBMITTER: Basson J

PROVIDER: S-EPMC4543586 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Influence of Smoking Status and Intensity on Discovery of Blood Pressure Loci Through Gene-Smoking Interactions.

Basson Jacob J Sung Yun Ju YJ de las Fuentes Lisa L Schwander Karen K Cupples L Adrienne LA Rao D C DC

Genetic epidemiology 20150503 6

<h4>Background</h4>Genetic variation accounts for approximately 30% of blood pressure (BP) variability but most of that variability has not been attributed to specific variants. Interactions between genes and BP-associated factors may explain some "missing heritability." Cigarette smoking increases BP after short-term exposure and decreases BP with longer exposure. Gene-smoking interactions have discovered novel BP loci, but the contribution of smoking status and intensity to gene discovery is u ...[more]

PMID: 25940791

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Project description:Alcohol consumption is a known risk factor for hypertension, with recent candidate studies implicating gene-alcohol interactions in blood pressure (BP) regulation. We used 6882 (predominantly) Caucasian participants aged 20-80 years from the Framingham SNP Health Association Resource (SHARe) to perform a genome-wide analysis of SNP-alcohol interactions on BP traits. We used a two-step approach in the ABEL suite to examine genetic interactions with three alcohol measures (ounces of alcohol consumed per week, drinks consumed per week, and the number of days drinking alcohol per week) on four BP traits [systolic (SBP), diastolic (DBP), mean arterial (MAP), and pulse (PP) pressure]. In the first step, we fit a linear mixed model of each BP trait onto age, sex, BMI, and antihypertensive medication while accounting for the phenotypic correlation among relatives. In the second step, we conducted 1 degree-of-freedom (df) score tests of the SNP main effect, alcohol main effect, and SNP-alcohol interaction using the maximum likelihood estimates (MLE) of the parameters from the first step. We then calculated the joint 2 df score test of the SNP main effect and SNP-alcohol interaction using MixABEL. The effect of SNP rs10826334 (near SLC16A9) on SBP was significantly modulated by both the number of alcoholic drinks and the ounces of alcohol consumed per week (p-values of 1.27E-08 and 3.92E-08, respectively). Each copy of the G-allele decreased SBP by 3.79 mmHg in those consuming 14 drinks per week vs. a 0.461 mmHg decrease in non-drinkers. Index SNPs in 20 other loci exhibited suggestive (p-value ≤ 1E-06) associations with BP traits by the 1 df interaction test or joint 2 df test, including 3 rare variants, one low-frequency variant, and SNPs near/in genes ESRRG, FAM179A, CRIPT-SOCS5, KAT2B, ADCY2, GLI3, ZNF716, SLIT1, PDE3A, KERA-LUM, RNF219-AS1, CLEC3A, FBXO15, and IGSF5. SNP-alcohol interactions may enhance discovery of novel variants with large effects that can be targeted with lifestyle modifications.

Project description:Smoking status does not indicate the amount or length of tobacco use, and thus, it is an imperfect measure to assess the association between cigarette smoking and severe coronavirus disease 2019 (COVID-19) outcomes. This investigation assessed whether cigarette smoking status, intensity of smoking (i.e., average daily packs of cigarettes smoked), duration of smoking, and pack-years of smoking are associated with severe outcomes among adults diagnosed with COVID-19. We conducted a retrospective, cross-sectional study in which we identified consecutive patients diagnosed with COVID-19 at the University of Cincinnati healthcare system between 13 March 2020 and 30 September 2020 who had complete information on smoking status, severe COVID-19 outcomes, and covariates (i.e., demographics and comorbidities). We used logistic regression to evaluate the associations of smoking status and intensity of smoking with COVID-19 severity, defined as hospitalization, admission to intensive care unit (ICU), or death, adjusting for sociodemographics and comorbidities. Among the 4611 COVID-19 patients included in the analysis, 18.2% were current smokers and 20.7% were former smokers. The prevalence of COVID-19 outcomes was 28.9% for hospitalization, 9.8% for ICU admission, and 1.4% for death. In the adjusted analysis, current smoking (AOR: 1.23, 95% CI: 1.02-1.49), former smoking (AOR: 1.28, 95% CI: 1.07-1.54), and pack-years of smoking (AOR: 1.09, 95% CI: 1.02-1.17) were associated with a higher prevalence of hospitalization. Average daily packs of cigarettes smoked was associated with a higher prevalence of hospitalization (AOR: 1.30, 95% CI: 1.10-1.53) and ICU admission (AOR: 1.23, 95% CI: 1.04-1.44). Smoking status, pack-years, and intensity of smoking were associated with hospitalizations in patients with COVID-19 and intensity of smoking was associated with ICU admission. The findings underscore the need for detailed information beyond smoking status when evaluating smokers with COVID-19 so that the potential for adverse sequelae may be optimally managed in at-risk patients.

Dataset Information

Influence of Smoking Status and Intensity on Discovery of Blood Pressure Loci Through Gene-Smoking Interactions.

Publications

Influence of Smoking Status and Intensity on Discovery of Blood Pressure Loci Through Gene-Smoking Interactions.

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